Administration of anastrazole, an aromatase inhibitor, reduces the protective effects of testosterone treatment in an animal model of amyotrophic lateral sclerosis

MEYER M; ROIG P; ESPERANTE I; LIMA A; GONZÁLEZ DENISELLE, M. C; LARA A; DE NICOLA, A. F.

Congreso; Reunion de la sociedad Argentina de Investigacion Clinica; 2021

Amyotrophic   lateral  sclerosis (ALS) is characterized by progressive degeneration of upperand lower motoneurons leading to muscle weakness and motor impairment. The Wobbler (WR) mouse, a recognizedmodel of ALS, shows a selective loss of motoneurons, astrocytosis andmicrogliosis in cervical spinal cord (CSC). ALS presentsin men atyounger ages than women, but increases after menopause. Testosterone (T) exerts its effects via androgen (AR), orestrogen receptors after bioconversion into several metabolites. Previous work has shown that T reduces gliosisand improves clinical score in male WRs. Now, we investigated the effects of cotreatment of T + anastrazole, an aromatase inhibitor (AI),on: 1) mRNA expression of myelin oligodendrocyte glycoprotein (MOG) andproteolipid protein (PLP)- 2) CD11B mRNA, a marker of microglia, 3) %AR-immunoreactive (IR) cells in ventral horn. T was implanted in 10mm silastic tubes for 2 months. AI was given in DMSO 10% by Alzet osmotic pumps(1mg/kg/day) s.c. starting 1 week before T. Four groups were prepared:a) WRs or (b) controls receiving empty silastictubes + vehicle-pumps, c) WR+T (silastic tubes filled with T) + vehicle-pumps and d) WR+T+AI. Pituitary weight, a glandsensitive to estradiol, is greater in WRs (p<0.05 vs. control) and smallerin WR+T+AI (p<0.05 vs WR). MOG mRNA rose in WR+T (p<0.05 vs WR) but not PLP.However, both myelin genes were significantly reduced in WR+T+AI (p <0.01vs. WR+T). CD11B was reduced by T in WRs (p<0.05 vs. WR), but WRs andWR+T+AI showed higher expression (p<0.05 vs. controls or WR+T). The % AR-IRcells were low in WRs and WRs+T+AI (p<0.01 vs. controls), but increased in WR+T(p<0.01 vs WR). The mRNA for the steroidogenic acute regulatory protein(StAR) increased in WRs (p<0.05 vs control) and was still higher in WR+T andWR+T+AI (p <0.05; p <0.01 vs WRs). These data support that estrogen-derived aromatase may play a role inandrogen neuroprotection.